Tissue plasminogen activator (tPA) activity is a novel and early marker of asymptomatic LEAD in type 2 diabetes.

INTRODUCTION: Lower extremity arterial disease (LEAD) is often one of the first signs of a generalized atherosclerotic disease in type 1 and type 2 diabetic subjects. MATERIALS AND METHODS: We studied 143 diabetic subjects at 30-70 years of age, M/F 69/74, 74 with type 1 and 69 with type 2 diabetes, without previously known or suspected lower extremity arterial disease. The relationship between early asymptomatic lower extremity arterial disease and blood levels of HbA1c, lipids and fibrinolysis markers (tPA-activity, tPA mass, PAI-1 activity, tPA-PAI-1 complex) was assessed. In parallel, a group with non-diabetic subjects (n=80) was studied. RESULTS: 35 (24%) diabetic subjects were classified as having sign(s) of LEAD, defined as having at least one reduced peripheral blood pressure measurement, 28% in type 1 vs 20% in type 2 diabetic subjects (p=NS). In univariate logistic regression analyses age, glycemic level (HbA1c), male gender (only in type 1 diabetic subjects), hypertension and tPA activity (only in type 2 diabetic subjects) were positively associated with LEAD. When markers of fibrinolysis were entered into a multivariate model adjusting for age, hypertension, and HbA1c, only tPA activity remained independently associated with LEAD (p=0.01) and this was also found in type 2 diabetic subjects (p=0.05). In type 1 diabetic subjects the increase in odds ratio was non-significant. CONCLUSIONS: Tissue plasminogen activator (tPA) activity may be an independent and early marker for asymptomatic lower extremity arterial disease in diabetic subjects, particularly in type 2 diabetes. Thus an altered fibrinolytic activity could be an early marker of atherosclerosis development in the lower extremities but the cause-effect relationship remains unclear.

Evaluation of simple non-invasive techniques for assessment of lower extremity arterial disease.

OBJECTIVE: To evaluate the reproducibility and precision of three, simple, non-invasive methods to measure blood pressure (BP) in the lower extremities by comparing reproducibility and sensitivity in finding abnormally low BP between ankle blood pressure (ABP) and toe blood pressure (TBP), by studying the concordance between TBP in toe 1 and 2 and evaluating the pole-pox method in patients with diabetes and lower extremity arterial disease (LEAD). SUBJECTS AND METHODS: The BP was measured twice, 1 week apart, in arms and legs in 13 controls and 12 patients with diabetes. ABP was assessed by using a Doppler pen for pulse registration. TBP was obtained by using a small cuff and a pulse oximetry sensor at toe 1 and 2. In eleven patients with diabetes and previously known LEAD ABP was obtained through the pole-pox method. RESULTS: No significant difference in reproducibility between absolute BPs and indices (coefficients of variation <9%) was found. A non-significant improvement with 4-8% in the sensitivity in detecting LEAD was seen when BP indices were used instead of absolute BP. A significant correlation in the variation over time for systemic and TBP (r = 0.34, P = 0.015) and a strong correlation was found between TBP measured at toe 1 and 2, respectively (r = 0.99, P < 0.001) was found. TBP measured with pole-pox method were significantly correlated with measurements made by the ordinary cuff technique (r = 0.75, P < 0.001). CONCLUSIONS: The use of TBP and ABP indices instead of absolute BP does not improve the reproducibility but may improve the sensitivity with respect to detection of LEAD, especially in patients with diabetes. The pole-pox method may be used as an alternative screening method in patients with diabetes and LEAD.

Assessment of toe blood pressure is an effective screening method to identify diabetes patients with lower extremity arterial disease.

The authors evaluated a screening program for lower extremity arterial disease (LEAD) in diabetic patients and focused on the value of toe blood pressure assessment. They recruited 437 subjects, ages 30-70 years (134 healthy controls, 166 type 1 and 137 type 2 diabetic patients; control [Ctr], DM1, and DM2) with no previous history of LEAD. They were enrolled in a longitudinal study with a planned follow-up of 10 years. Patients were consecutively enrolled from outpatient diabetes units of 2 university hospitals. Subjects were screened with respect to peripheral circulation by use of established noninvasive techniques. These included arm, ankle (AP), and toe (TP) blood pressure measurements; evaluation of peripheral neuropathy; and a standardized physical examination. Results from the baseline examination are presented in this report. The number of patients who presented peripheral pressures or indices below normal (< mean -2 SD for controls) was higher among diabetic patients; 24% of DM1 and 31% of DM2, as compared to 6% of Ctr, had at least 1 lower limb with a low TP, AP, toe/arm index (TI), or ankle/arm index (AI), and these subjects were mainly identified by using the toe/arm index. TI was independently and negatively associated with fasting blood glucose in both patient groups, and with smoking, age, and diabetes duration in DM1. The mean AP was higher in the DM1 and DM2 groups compared to Ctr, whereas overall TP, TI, and AI were similar in the groups. It was also shown that abnormally low TI was significantly more common than low AI among diabetics (p<0.001), and this was true for TP vs AP as well (p<0.05). It is beneficial to include assessment of toe blood pressure and toe/arm blood pressure index to detect early LEAD in diabetic patients. Ankle blood pressure and indices alone are less efficient, owing probably to medial sclerosis in diabetic patients. Up to 30% of diabetic patients with no ischemic symptoms may have signs of impaired arterial circulation.